CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

Methods: In this population-based retrospective cohort study, we used routinely collected data from the District Health Information System 2, which included over 4.6 million people screened for HBV from January 2016 to June 2023. During this period, individuals were included if they were >2 years old. The HBV care cascade was analyzed across six stages: (1) lifetime prevalence, (2) diagnosis, (3) enrolled in care, (4) eligible to treatment, (5) treatment initiation, and (6) treatment continuation. Infection was defined as presence of at least one reactive hepatitis B surface antigen (HBsAg). Lifetime prevalence was estimated as the sum of diagnosed and estimated undiagnosed cases. Hierarchical logistic regression was used to identify progression-related factors through the different cascade stages. Results: Among 4,604,468 individuals screened, 57,520 tested positive for HBsAg, of which 52,827 (91.8%) had HBV mono-infection and 4,693 (8.2%) were co-infected with HIV. Of those diagnosed, 21,247 (37.0%) were enrolled in care, and 6,429 (30.3%) of the enrolled individuals were eligible for treatment. Of those eligible, 4,893 (76.1%) initiated treatment, and 4,839 (98.9%) were retained on treatment at one-year post-initiation. Individuals aged 35–54 were more likely to engage in care (adjusted odds ratio [aOR], 1.19; 95% CI: 1.12–1.27), initiate treatment (aOR, 1.45; 95% CI: 1.14–1.86), and be retained on treatment (aOR, 2.88; 95% CI: 1.09–7.63) compared to those under 35. Individuals living 30 minutes to 1 hour from a health facility were less likely to engage in care or remain on treatment compared to those living closer to a facility. Conclusions: Overall, engagement with care was low, which highlights the need to strengthen awareness among general population regarding HBV prevention and control. Younger individuals and those living farther from health facilities are less likely to engage in care and remain on treatment. Strengthening lower-level health facilities by expanding the number of trained healthcare providers and improving infrastructure is critical to enhance HBV prevention and treatment at the community level.

undetectable HBV DNA, all had HIV RNA <20 cp/ml, and NUC duration was 8.1 years (7.0 - 9.1). We analyzed 54,250 genes across 25,109 cell spots. LMER on HBV+ hepatocytes (spots) among EP identified 727 upregulated and 76 downregulated host genes (mean fixed effect + 6SD, adjusted p-value < 0.05). The expression pattern of the top 50 significant genes varied with NUC duration, showing higher expression in hepatocytes from EP with long-term NUC. These genes comprised several enriched pathways crucial to liver function, such as the lipid metabolic process (adjusted p-value = 1.6e-05, fold enrichment = 10.64). Furthermore, immune response pathways to viral infection were enriched, highlighted by 15 upregulated genes (e.g., C3, APOA1). Enriched lymphocyte markers surrounding HBV-transcribing hepatocytes were identified in EP with the longest antiviral treatment and in most EN compared to those EP with short-term treatment. Notably, the post-biopsy HBeSC EP with short-term NUC exhibited pronounced expression of these markers around HBV+ hepatocytes. Conclusions: Spatial transcriptomics of liver from PWHHB reveals that HBV transcription was closely associated with host metabolic processes and immune responses. These findings underscore intricate dynamics between HBV and host cellular machinery, yielding putative genes and pathways affecting HBV transcription.

Oral Abstracts

112

Highly Durable Seroprotection With HepB-CpG Vaccine in People With HIV (PWH): ACTG A5379 (BEeHIVe) Kristen Marks 1 , Minhee Kang 2 , Triin Umbleja 2 , Andrea Cox 3 , Anchalee Avihingsanon 4 , Patcharaphan Sugandhavesa 5 , Leolin Katsidzira 6 , Josphat Kosgei 7 , Hugo Perazzo 8 , Jennifer Price 9 , Stephanie R. Caruso 10 , Kevin Knowles 10 , Beverly Alston-Smith 11 , Parita Rathod 12 , Kenneth E. Sherman 13 , for the ACTG A5379 (BEeHIVe) Study Team 1 Weill Cornell Medicine, New York, NY, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 HIV-NAT, Thai Red Cross AIDS and Infectious Disease Research Centre, Bangkok, Thailand, 5 Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand, 6 University of Zimbabwe, Harare, Zimbabwe, 7 Walter Reed Project–Kericho, Kericho, Kenya, 8 Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, 9 University of California San Francisco, San Francisco, CA, USA, 10 Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA, 11 Division of AIDS, Bethesda, MD, USA, 12 DLH Corporation, Atlanta, GA, USA, 13 University of Connecticut Health Center, Farmington, CT, USA Background: A5379 primary analysis demonstrated that 2- and 3-dose HepB-CpG (2-CpG, 3-CpG) achieved superior seroprotective response (SPR defined as anti-HBs ≥10 mIU/mL) compared to 3-dose HepB-alum (3-alum) in PWH with prior HBV vaccine non-response (Group A), and 100% SPR was achieved with 3-CpG in vaccine-naïve PWH (Group B). SPR durability is now evaluated. Methods: A5379 evaluated immunogenicity of HepB-CpG in PWH on ART with CD4 ≥100 cells/mm 3 and HIV-1 RNA <1000 copies/mL. Group A was randomized 1:1:1 to: 2-CpG intramuscularly (IM) (20 mcg recombinant HBsAg, 3000 mcg CpG 1018® adjuvant) at Wks 0 and 4; 3-CpG IM at Wks 0, 4, 24; or 3-alum IM (20 mcg recombinant HBsAg) at Wks 0, 4, 24. All Group B participants received 3-CpG. End of study anti-HBs was assessed at Wk72 (48 wks after 3-dose, 68 wks after 2-dose) regardless of visit window. SPR proportion differences in Group A were estimated with two-sided 97.5% Newcombe CI, stratified by sex at birth and diabetes status. Otherwise, 95% Wilson CIs were used.

111

Intrahepatic Transcriptomics in HBV-HIV Co-Infection Uncover Host Responses to HBV Transcription Che-Min Lo 1 , Ruzhang Zhao 2 , Wentao Zhan 2 , Hongkai Ji 2 , Chloe Thio 1 , Ashwin Balagopal 1 1 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Background: Liver disease due to viral hepatitis is a leading cause of mortality in PWH. Elucidating host genes that affect HBV transcription may accelerate hepatitis B virus (HBV) cure discovery. We hypothesized that host genes modulate HBV transcription during nucleos(t)ide analogue (NUC) therapy. Methods: We used mRNA-capture slides (10X Genomics) on liver biopsies from 14 people with HIV and CHB (PWHHB) to sequence 100-250 million read-pairs per sample (Illumina NovaSeq 6000). Reads were mapped to a custom human+HBV reference. After quality control, we applied robust cell-type decomposition within gene expression spots to identify hepatocytes where HBV replicates and immune cell populations. We applied linear mixed effects regression (LMER) using HBV RNA as a covariate to identify host genes associated with HBV transcription. Pathway analysis was performed. Results: Among 7 HBeAg-positive (EP) PWHHB, median values were: HBV DNA (Log 10 IU/ml) 4.1, HIV RNA <20 cp/ml, duration of NUCs 7 years (0.1 - 12.5); 1 participant was treatment-naïve and 1 underwent rapid HBeAg seroconversion (HBeSC) post-biopsy. Among 7 HBeAg-negative (EN) PWHHB, all but one had

19

CROI 2025